d'Uscio L V, Barton M, Shaw S, Lüscher T F
Institute of Physiology, University of Zürich and University Hospital, Switzerland.
J Cardiovasc Pharmacol. 2000;35(4 Suppl 2):S55-59. doi: 10.1097/00005344-200000002-00013.
Endothelin (ET)-1, a potent vasoconstrictor peptide, is primarily released abluminally from endothelial cells and exerts its biological effect through the activation of specific ET receptors. Endothelin subtype A receptors (ET(A)) are involved in constriction and proliferation of vascular smooth muscle cells, whereas endothelin subtype B receptors (ET(B)) on endothelial cells mediate the formation of nitric oxide, which acts as vasodilator and inhibits platelet aggregation. Cardiovascular risk factors such as hypertension and aging, as well as hypercholesterolemia, which are precursors of atherosclerosis, and elevated ET-1 levels are found. The best approach to determine the contribution of endogenous ET to vascular structural and functional alterations can be achieved by chronic inhibition of ET receptors with ET receptor antagonists. Recent studies showed favourable effects of selective ET(A)-antagonists on vascular alterations in different experimental models of hypertension, hypercholesterolemia and atherosclerosis, suggesting that activation of the local ET system importantly contributes to endothelial dysfunction and vascular remodeling, mainly through ET(A) receptors. Chronic blockade of ET(A) receptors may be a new therapeutic approach for the treatment of atherosclerosis and its risk factors.
内皮素（ET）-1是一种强效血管收缩肽，主要从内皮细胞的管腔外释放，并通过激活特定的ET受体发挥其生物学效应。内皮素A型受体（ET(A)）参与血管平滑肌细胞的收缩和增殖，而内皮细胞上的内皮素B型受体（ET(B)）介导一氧化氮的形成，一氧化氮作为血管舒张剂并抑制血小板聚集。发现存在心血管危险因素，如高血压、衰老以及作为动脉粥样硬化先兆的高胆固醇血症，且内皮素-1水平升高。通过用ET受体拮抗剂长期抑制ET受体，可以实现确定内源性ET对血管结构和功能改变作用的最佳方法。最近的研究表明，选择性ET(A)拮抗剂在高血压、高胆固醇血症和动脉粥样硬化的不同实验模型中对血管改变具有有利作用，这表明局部ET系统的激活主要通过ET(A)受体对内皮功能障碍和血管重塑起重要作用。长期阻断ET(A)受体可能是治疗动脉粥样硬化及其危险因素的一种新的治疗方法。
